ABSTRACT

After 20 years of screening for breast and prostate cancer, several observations can be made. First, the incidence of these cancers increased after the introduction of screening but has never returned to prescreening levels. Second, the increase in the relative fraction of early stage cancers has increased. Third, the incidence of regional cancers has not decreased at a commensurate rate. One possible explanation is that screening may be increasing the burden of low-risk cancers without significantly reducing the burden of more aggressively growing cancers and therefore not resulting in the anticipated reduction in cancer mortality. To reduce morbidity and mortality from prostate cancer and breast cancer, new approaches for screening, early detection, and prevention for both diseases should be considered.

Figures

Figure 1. Hypothetical Screening Scenarios

Three hypothetical scenarios of changes over time in stage-specific incidence rates associated with widespread screening usage are presented. The dotted lines indicate the point of screening initiation. The fraction of localized and regional disease before and after screening is shown for each scenario. A, Screening leads to an increase in localized cancers, a decrease in regional cancers, and stable rates of overall invasive cancer (after an initial increase following introduction of screening). B, Screening leads to an increase in the detection of total and early stage cancers but without a decrease in the rate of regional cancers. C, Screening results in an increase in early and overall cancer rates, with some decrease in regional stage disease. This outcome is intermediate between A and B. D, The incidence of localized and regional cancers is shown for the prescreening period and for each of the scenarios. The height of the bars represents total incidence. E, The relative percentage of localized vs regional cancers is shown. Note that all 3 scenarios lead to the same increase in the percentage of detection of localized cancers.

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Figure 2. Age-Adjusted Incidence Rates of Breast and Prostate Cancer Over Time and by Prescreen and Postscreen Snapshot

A, Age-adjusted incidence rate by stage of invasive female breast cancers for all ages, SEER 1973-2006.8 Mammography was introduced in 1983 and more widely used beginning in 1986.9 The incidence per 100 000 women of localized, regional, and metastatic breast cancer is shown over time (left), and for the period prior to the uptake of screening (1982) and 16 years after (1998) (middle). Local disease, as a fraction of all cancers reported, is shown on the right. B, Age-adjusted incidence rate of adenocarcinoma of the prostate for men older than 24 years, SEER, 1973-2006. Prostate cancer screening began in 1986 and was more widely used beginning in 1989-1990. Given the degree of missing data for prostate cancer TNM stage in SEER, we chose to show the change in Gleason grade, a significant predictor of outcome since the introduction of screening. The middle panel shows the incidence per 100 000 men of tumors with Gleason grades that were low- and intermediate-grade (2-7) vs high-grade (8-10) tumors, for the period prior to the uptake of screening (1988) and 16 years after (2004). The low- and intermediate-grade tumors as a fraction of all cancers is shown in the panel on the right.10

Growth rates of 4 tumors are displayed from the time the first tumor cells appear while the tumor is not yet detectable (microscopic); when it can be detected as localized (confined to the organ) and most likely to be curable; regional (after the tumor spreads beyond the organ) where it may not be curable; and to the point when metastases and death occur. Tumor A remains undetectable and without morbidity during the patient's lifetime. Tumor B grows until it becomes detectable but never causes symptoms or leads to death. Both tumors A and B represent low-risk indolent or IDLE (indolent lesions of epithelial origin) tumors. Tumor C is destined to become metastatic and fatal but can be detected while still curable. Tumor D is destined to become metastatic but grows so quickly that by the time it can be detected, it may no longer be curable. Among these 4 tumors, only the patient with tumor C benefits from screening.

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Figure 4. Framework for Advancing Screening and Detection

At point 1, it would be optimal to find a biomarker for susceptibility (eg, breast density, risk models, gene polymorphisms, immune function) to tailor recommendations for screening. At point 2, higher-risk patients would undergo detection screening with imaging, biomarkers, or both. When a cancer is detected, point 3, molecular profiling determines tumor type, and risk for progression. Minimal-risk disease can be treated less aggressively, and patients with significant risk of metastatic disease should receive tailored interventions, point 4. Biomarkers that predict good response to therapy with targeted agents should provide opportunities to develop tailored prevention interventions with potential biomarkers for measuring response, point 5. Patients with poor response to therapy should provide clues for identifying markers of risk and susceptibility and research should be directed to identify those susceptible (point 6) to aggressive disease that is difficult to treat. Tailored screening might include susceptibility biomarkers or more intensive detection strategies (eg, magnetic resonance imaging for BRCA carriers). Biomarkers that characterize tumor type and response should inform prevention and screening efforts (pathways shown in blue).

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